title: Tyrosinase inhibition by isophthalic acid: kinetics and computational simulation.
abstract: Using inhibition kinetics and computational simulation, we studied the reversible inhibition of tyrosinase by isophthalic acid (IPA). IPA inhibited tyrosinase in a complex manner with K(i)=17.8 ± 1.8mM. Measurements of intrinsic and ANS-binding fluorescence showed that IPA induced no changes in tertiary protein structure. For further insight, we predicted the 3D structure of tyrosinase and used a docking algorithm to simulate binding between tyrosinase and IPA. Simulation was successful (binding energies for Dock6.3: -25.19 kcal/mol and for AutoDock4.2: -4.28 kcal/mol), suggesting that IPA interacts with PRO175 or VAL190. This strategy of predicting tyrosinase inhibition based on hydroxyl group number and orientation may prove useful for the screening of potential tyrosinase inhibitors.
authors.affiliation: College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo 315100, PR China.
authors.forename: Yue-Xiu
authors.initials: YX
authors.lastname: Si
authors.forename: Shang-Jun
authors.initials: SJ
authors.lastname: Yin
authors.forename: Daeui
authors.initials: D
authors.lastname: Park
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Lü
authors.forename: Hai-Meng
authors.initials: HM
authors.lastname: Zhou
authors.forename: Jun-Mo
authors.initials: JM
authors.lastname: Yang
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Qian
authors.forename: Yong-Doo
authors.initials: YD
authors.lastname: Park
mesh_terms: D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005453:Fluorescence; D007700:Kinetics; D008958:Models, Molecular; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D010795:Phthalic Acids / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D010795:Phthalic Acids; C059768:isophthalate; D014442:Monophenol Monooxygenase